摘要
目的 分析遗传性非腺瘤病性结直肠癌 ( hereditary non- polyposis colorectal cancers ,HN-PCC)结肠腺瘤病 ( adenomatous polyposis coli,APC)基因突变的特点及错配修复缺陷对其影响。方法采用体外蛋白合成试验和序列分析确定 19例 HNPCC病例 APC体细胞突变。结果 19例病例中有 11例( 13个突变点 )发生 APC突变 ,发生率为 5 8% ( 11/ 19) ,其中移码突变 9个 ,无义突变 4个 ,移码突变占多数( 6 9% )。所有移码突变表现为 1～ 2个碱基的缺失或插入 ,大多 ( 7/ 9)发生在简单核苷酸重复序列 ,特别是单腺苷酸重复序列 ( A) n( 5 / 9)。检出的由单个碱基替换而导致的无义突变都发生在 Cp G岛 ,表现为 C向 T的转换。结论 多于半数的 HNPCC发生 APC突变 ,其突变多发生在编码区单核苷酸重复序列 (移码突变 )或 Cp G岛 (点突变 )上 ,提示 APC基因失活在 HNPCC为常见的分子事件 ;错配修复缺陷所致的微卫星DNA不稳定性等内源性机理可能对
Objective: To analyze the mutational features of adenomatous polyposis coli (APC) gene and to explore the effect of mismatch repair (MMR) deficiency on its mutations in hereditary nonpolyposis colorectal cancers (HNPCC). Methods: PCR-based in-vitro synthesized protein test (IVSP) assay and sequencing analysis were used to confirm somatic mutations of whole APC gene in 19 HNPCC patients. Results: Eleven cases with thirteen mutations were determined. The frequency of APC mutation was 58% (11/19). The exhibiting mutations consisted of 9 frameshift mutations and 4 nonsense ones, indicating the existence of more frameshift mutations (69%). All of frameshift mutations were deletion or insertion of 1-2 bp and most of them (7/9) happened at simple nucleotide repeat sequences, particularly within (A)n tracts (5/9). All of four nonsense mutations resulted from C to T transitions at CpG sites. Conclusion: Mutational inactivations of APC gene were detected in more than half of HNPCC patients in this study, indicating that APC mutation is a common molecular event in the tumorigenesis of HNPCC. According to the location of frameshift mutations at simple nucleotide repeat sequences and point mutations at CpG sites, it was suggested that endogenous mechanisms like MMR deficiency might exert an effect on the nature of APC mutations in most HNPCC.
出处
《中华医学遗传学杂志》
EI
CAS
CSCD
2003年第3期196-199,共4页
Chinese Journal of Medical Genetics
基金
国家自然科学基金 (3960 0 0 55)
教育部出国留学人员回国启动基金
浙江省教育厅课题~~
